The history of Parkinson's disease: early clinical descriptions and neurological therapies

Abstract

Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease.

Figure 1.

Essay on the Shaking Palsy. James Parkinson's short monograph is the first clear medical document dealing with Parkinson's disease (Parkinson 1817).

Figure 2.

Charcot and “myographic curves.” (Left) French neurologist Jean-Martin Charcot (1825–1893). (Right) Semi-diagrammatic “myographic curves” published by Charcot in 1887. The top tracing represents an intention tremor in multiple sclerosis. Segment AB indicates “at rest,” and BC indicates increasing oscillations during voluntary movement. The lower tracing represents a Parkinsonian tremor, with segment AB indicating a tremor at rest, which persists in segment BC during voluntary movement. Charcot’s graphical recording method on which these drawings were based is not described, but in other circumstances he relied on various pneumatic tambour-like mechanisms (Charcot 1872; Goetz 1987).

Figure 3.

Atypical Parkinsonism. (A) Drawing from Charcot’s original lesson, given on June 12, 1888, in which he contrasted a typical Parkinson's disease showing a flexed posture (left) with a Parkinsonian variant that included the absence of tremor and extended posture (right). Charcot regularly taught his students by comparing and contrasting cases of patients from the Salpêtrière inpatient and outpatient services. (B) Four drawings by Charcot from his lesson on atypical Parkinson's disease, dated June 12, 1888, showing the distinctive facial features of his patient, Bachère, showing forehead muscles and superior orbicularis in simultaneous contraction, activation of the palpebral portion of the orbicularis and combined activation of the frontalis superior portion of the orbicularis and platysma, giving a frightened expression in contrast to the placid, blank stare of typical Parkinson's disease patients. This case is a compelling case of likely progressive supranuclear palsy (Goetz, 1987; Charcot 1888a).

Figure 4.

Early treatment of Parkinson's disease. Prescription dated 1877 from the College of Physicians of Philadelphia Library. In treating Parkinson's disease, Charcot used belladonna alkaloids (agents with potent anticholinergic properties) as well as rye-based products that had ergot activity, a feature of some currently available dopamine agonists. Charcot’s advice was empiric and preceded the recognition of the well-known dopaminergic/cholinergic balance that is implicit to normal striatal neurochemical activity (Charcot 1872).

Figure 5.

Vibratory therapy. Charcot observed that patients with Parkinson's disease experienced a reduction in their rest tremor after taking a carriage ride or after horseback riding. He developed a therapeutic vibratory chair that simulated the rhythmic shaking of a carriage (Goetz 1996). A vibratory helmet to shake the head and brain was later developed. Such therapies were not used widely but the availability of modern medical vibratory chairs offers an opportunity to confirm or refute Charcot’s observation.

Figure 6.

Early surgical interventions. (Left) Victor Horsley (1857–1916) was a celebrated British surgeon who attempted a surgical intervention on a movement disorder patient with athetosis in 1909. He excised motor cortex with substantial improvement in involuntary movements. (Middle) Working in London with his physiologist colleague, Robert Henry Clarke (1850–1926), he developed early stereotaxic equipment, first for animal experiments and then for humans. (Right) This daunting surgical apparatus taken from their reports in Brain in 1908 guided them to deep brain centers including the basal ganglia and the cerebellum (Horsley and Clarke 1908).